Evidence of an Antigen Presenting Cell Phenotype in Granular Cell Tumours

Granular Cell Tumours (GCTs) are rare subepithelial lesions that are believed to develop from Schwann cells and are characterized by large polygonal cells with abundant lysosomes. Pilot studies from our laboratory showing unexpected HLA-DR immunoreactivity in GCTs lead us to hypothesize that GCTs have an antigen presenting cell (APC) phenotype. To test our hypothesis, we assessed immunoreactivity of GCT lesions to APC phenotype markers, including CD68, HLA-DR, CD163, CD40 and CD11c. In addition, we assessed markers of neural crest cell (NCC) origin S100, SOX10, NSE and GAP43. Samples subjected to these studies included 23 cases of GCTs and 10 cases of Schwannomas, used as comparators. To confirm the key findings, we detected transcript levels of select genes using quantitative polymerase chain reaction. We identified a new NCC marker for GCTs, GAP43. We also provide evidence of an APC phenotype of GCTs, as determined from CD68 and HLA-DR immunoreactivity. Due to the limited nucleic acid yield from paraffin-embedded GCT sections, we were unable to draw conclusions from transcript assessment

Misato Controls Mitotic Microtubule Generation by Stabilizing the TCP-1 Tubulin Chaperone Complex

Mitotic spindles are primarily composed of microtubules (MTs), generated by polymerization of α- and β-Tubulin hetero-dimers. Tubulins undergo a series of protein folding and post-translational modifications in order to fulfill their functions. Defects in Tubulin polymerization dramatically affect spindle formation and disrupt chromosome segregation. We recently described a role for the product of the conserved misato (mst) gene in regulating mitotic MT generation in flies, but the molecular function of Mst remains unknown. Here, we use affinity purification mass spectrometry (AP-MS) to identify interacting partners of Mst in the Drosophila embryo. We demonstrate that Mst associates stoichiometrically with the hetero-octameric Tubulin Chaperone Protein-1 (TCP-1) complex, with the hetero-hexameric Tubulin Prefoldin complex, and with proteins having conserved roles in generating MT-competent Tubulin. We show that RNAi-mediated in vivo depletion of any TCP-1 subunit phenocopies the effects of mutations in mst or the Prefoldin-encoding gene merry-go-round (mgr), leading to monopolar and disorganized mitotic spindles containing few MTs. Crucially, we demonstrate that Mst, but not Mgr, is required for TCP-1 complex stability and that both the efficiency of Tubulin polymerization and Tubulin stability are drastically compromised in mst mutants. Moreover, our structural bioinformatic analyses indicate that Mst resembles the three-dimensional structure of Tubulin monomers and might therefore occupy the TCP-1 complex central cavity. Collectively, our results suggest that Mst acts as a co-factor of the TCP-1 complex, playing an essential role in the Tubulin-folding processes required for proper assembly of spindle MTs

Gas-Driven Fracturing of Saturated Granular Media

Multiphase flows in deformable porous materials are important in numerous geological and geotechnical applications, however the complex flow behaviour make subsurface transport processes difficult to control or even characterise. Here we study gas-driven (pneumatic) fracturing of a wet unconsolidated granular packing confined in a Hele-Shaw cell, and present an in-depth analysis of both pore-scale phenomena and large-scale pattern formation. The process is governed by a complex interplay between pressure, capillary, frictional and viscous forces. At low gas injection rate, fractures grow in a stick-slip fashion and branch out to form a simply connected network. We observe the emergence of a characteristic length-scale -- the separation distance between fracture branches -- creating an apparent uniform spatial fracture density. We conclude that the well defined separation distance is the result of local compaction fronts surrounding fractures, keeping them apart. A scaling argument is presented that predicts fracture density as a function of granular friction, grain size, and capillary interactions. We study the influence of gas injection rate, and find that the system undergoes a fluidisation transition above a critical injection rate, resulting in directional growth of fractures, and a fracture density that increases with increasing rate. A dimensionless Fluidisation number F is defined as the ratio of viscous to frictional forces, and our experiments reveal a frictional regime for F1) characterized by continuous growth in several fracture branches simultaneously

Institutional analysis of health promotion for older people in Europe - Concept and research tool

Background: European societies are ageing rapidly and thus health promotion for older people (HP4OP) is becoming an increasingly relevant issue. Crucial here is not only the clinical aspect of health promotion but also its organisational and institutional dimension. The latter has been relatively neglected in research on HP4OP. This issue is addressed in this study, constituting a part of the EU project ProHealth65+, engaging ten member countries. This paper is based on two intertwining research goals: (1) exploring which institutions/organisations are performing HP4OP activities in selected European countries (including sectors involved, performed roles of these institutions, organisation of those activities); (2) developing an institutional approach to HP4OP. Thus, the paper provides a description of the analytical tools for further research in this area. Methods: The mentioned aims were addressed through the mutual use of two complementary methods: (a) a literature review of scientific and grey literature; and (b) questionnaire survey with selected expert respondents from 10 European countries. The expert respondents, selected by the project's collaborating partners, were asked to fill in a custom designed questionnaire concerning HP4OP institutional aspects. Results: The literature review provided an overview of the organisational arrangements in different HP4OP initiatives. It also enabled the development of functional institutional definitions of health promotion, health promotion activities and interventions, as well as an institutional definition adequate to the health promotion context. The distinctions between sectors were also clarified. The elaborated questionnaires provided in-depth information on countries specifically indicating the key sectors involved in HP4OP in those selected countries. These are: health care, regional/local authorities, NGO's/voluntary institutions. The questionnaire and literature review both resulted in the indication of a significant level of cross-sectorial cooperation in HP4OP. Conclusions: The inclusion of the institutional analysis within the study of HP4OP provides a valuable opportunity to analyse, in a systematic way, good practices in this respect, also in terms of institutional arrangements. A failure to address this aspect in policymaking might potentially cause organisational failure even in evidence-based programmes. This paper frames the perception of this problem

Growth rates and the prevalence and progression of scoliosis in short-statured children on Australian growth hormone treatment programmes

STUDY DESIGN AND AIM: This was a longitudinal chart review of a diverse group (cohort) of patients undergoing HGH (Human Growth Hormone) treatment. Clinical and radiological examinations were performed with the aim to identify the presence and progression of scoliosis. METHODS AND COHORT: 185 patients were recruited and a database incorporating the age at commencement, dose and frequency of growth hormone treatment and growth charts was compiled from their Medical Records. The presence of any known syndrome and the clinical presence of scoliosis were included for analysis. Subsequently, skeletally immature patients identified with scoliosis were followed up over a period of a minimum four years and the radiologic type, progression and severity (Cobb angle) of scoliosis were recorded. RESULTS: Four (3.6%) of the 109 with idiopathic short stature or hormone deficiency had idiopathic scoliosis (within normal limits for a control population) and scoliosis progression was not prospectively observed. 13 (28.8%) of 45 with Turner syndrome had scoliosis radiologically similar to idiopathic scoliosis. 11 (48%) of 23 with varying syndromes, had scoliosis. In the entire cohort, the growth rates of those with and without scoliosis were not statistically different and HGH treatment was not ceased because of progression of scoliosis. CONCLUSION: In this study, there was no evidence of HGH treatment being responsible for progression of scoliosis in a small number of non-syndromic patients (four). An incidental finding was that scoliosis, similar to the idiopathic type, appears to be more prevalent in Turner syndrome than previously believed

Graphene on quartz modified with rhenium oxide as a semitransparent electrode for organic electronic

Our research shows that commercially available graphene on quartz modified with rhenium oxide meets the requirements for its use as a conductive and transparent anode in optoelectronic devices. The cluster growth of rhenium oxide enables an increase in the work function of graphene by 1.3 eV up to 5.2 eV, which guarantees an appropriate adjustment to the energy levels of the organic semiconductors used in OLED devices.Comment: 8 pages, 3 figure

EEG-neurofeedback and executive function enhancement in healthy adults: a systematic-review

EEG-neurofeedback training (EEG-NFT) is a promising technique that supports individuals in learning to modulate their brain activity to obtain cognitive and behavioural improvements. EEG-NFT is gaining increasing attention for its potential \u201cpeak performance\u201d applications on healthy individuals. However, evidence for clear cognitive performance enhancements with healthy adults is still lacking. In particular, whether EEG-NFT represents an effective technique for enhancing healthy adults\u2019 executive functions is still controversial. Therefore, the main objective of this systematic-review is to assess whether the existing EEG-NFT studies targeting executive functions have provided reliable evidence for NFT effectiveness. To this end, we conducted a qualitative analysis of the literature since the limited number of retrieved studies did not allow us meta-analytical comparisons. Moreover, a second aim was to identify optimal frequencies as NFT targets for specifically improving executive functions. Overall, our systematic review provides promising evidence for NFT effectiveness in boosting healthy adults\u2019 executive functions. However, more rigorous NFT studies are required in order to overcome the methodological weaknesses that we encountered in our qualitative analysis